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This page is still under construction. Salmonella Pathogenesis Salmonella is the causative agent for a wide range of diseases in humans, including gastroenteritis and enteric fever. Worldwide, Salmonella is estimated to cause over sixteen million cases of typhoid fever, resulting in approximately six hundred thousand deaths, and over one billion cases of acute gastroenteritis, resulting in approximately three million deaths, each year. Over five hundred genes in Salmonella are directly involved in pathogenesis. Yet, only a subset of these is expressed at a given time. Currently, an integrated model for differential gene expression is lacking. To address this problem, we are investigating how Salmonella dynamically regulates gene expression during the different phases of the infection cycle. By characterizing how these genes are coordinately expressed and regulated, we aim to understand the infection process and, more importantly, discover novel targets for antibiotics. Role of cross talk in regulating the dynamic expression of the flagellar Salmonella pathogenicity island 1 and type 1 fimbrial genes Journal of Bacteriology, 192(21):5767-77, 2010 Saini S, Slauch JM, Aldridge PD, Rao CV PubMed PDF The role of coupled positive feedback in the expression of the SPI1 type three secretion system in Salmonella PLoS Pathogens, 6(7):e1001025, 2010 Saini S, Ellermeier JR, Slauch JM, Rao CV PubMed PDF SprB is the molecular link between Salmonella pathogenicity island 1 (SPI1) and SPI4 Journal of Bacteriology, 192(9):2459-62, 2010 Saini S, Rao CV PubMed PDF The Salmonella SPI1 type three secretion system responds to periplasmic disulfide bond status via the flagellar apparatus and the RcsCDB system Journal of Bacteriology, 190(1):87-97, 2008 Lin D, Rao CV, Slauch JM PubMed PDF Designing orthogonal factors for regulating transcription and translation The goal of synthetic biology is to engineer and reprogram cellular processes for producing novel compounds and also improving health and the environment through the rational implementation of well-characterized genetic components. Introducing novel functionality into cells, however, requires components that do not interfere with native cellular processes. As we consider more complex synthetic biology applications, greater premium will be placed on expanding our genetic toolbox. Towards this goal, our lab has developed a set of computational algorithms for reprogramming the specificity of transcriptional factors and ribosomes in bacteria. In both cases, we were able to experimentally validate these algorithms. A central theme in both applications is the engineering of orthogonal pairs of regulatory factors, orthogonal in the sense that the engineered factor binds a sequence not recognized by the native factor but does not bind the sequences that are recognized by the native factor. Engineering transcription factors with novel DNA-binding specificity using comparative genomics Nucleic Acids Research, 37(8):2493-503, 2009 Desai TA, Rodionov DA, Gelfand MS, Alm EJ, Rao CV PubMed PDF Computational design of orthogonal ribosomes Nucleic Acids Research, 36(12):4038-46, 2008 Chubiz LM, Rao CV PubMed PDF Bacillus subtilis Chemotaxis We are investigating chemotaxis in the model Gram-positive bacterium Bacillus subtilis. While Escherichia coli has long been the paradigm for bacterial chemotaxis, the pathway architecture is not conserved in other species of bacteria. Interestingly, B. subtilis behaves in an identical manner to E. coli with regards to chemotaxis. The pathways in the two bacteria also have homologous proteins. Yet, how these proteins are “wired” to one another in the two pathways is entirely different. We seek to understand why these two pathways are “wired” differently and the extent of degeneracy in the basic design. Attractant binding induces distinct structural changes to the polar and lateral signaling clusters in Bacillus subtilis chemotaxis. Journal of Biological Chemistry, November 2010, Wu K, Walukiewicz HE, Glekas GD, Ordal GW, Rao CV PubMed Site-specific methylation in Bacillus subtilis chemotaxis: The effect of covalent modifications to the chemotaxis receptor McpB. Microbiology, September 2010, Glekas GD, Cates JR, Cohen TM, Rao CV, Ordal GW PubMed A PAS domain binds asparagine in the chemotaxis receptor McpB in Bacillus subtilis Journal of Biological Chemistry, 285(3):1870-8, 2010 Glekas GD, Foster RM, Cates JR, Estrella JA, Wawrzyniak MJ, Rao CV, Ordal GW PubMed PDF The molecular basis of excitation and adaptation during chemotactic sensory transduction in bacteria Contributions to Microbiology, 16:33-64, 2009 Rao CV, Ordal GW PubMed PDF The three adaptation systems of Bacillus subtilis chemotaxis Trends in Microbiology, 16(10):480-7, 2008 Rao CV, Glekas GD, Ordal GW PubMed PDF Phosphatase localization in bacterial chemotaxis: divergent mechanisms, convergent principles Physical Biology, 14;2(3):148-58, 2005 Rao CV, Kirby JR, Arkin AP PubMed PDF Design and diversity in bacterial chemotaxis: a comparative study in Escherichia coli and Bacillus subtilis PLoS Biology, 2(2):E49, 2004 Rao CV, Kirby JR, Arkin AP PubMed PDF